Cargando…
Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation
Endothelial cells play a critical role in the process of angiogenesis during skin wound healing. The migration and proliferation of endothelial cells are processes that are initiated by the hypoxic microenvironment in a wound, but the underlying mechanisms remain largely unknown. Here, we identified...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476958/ https://www.ncbi.nlm.nih.gov/pubmed/31040780 http://dx.doi.org/10.3389/fphar.2019.00368 |
_version_ | 1783412968325644288 |
---|---|
author | Zhang, Junhui Li, Lingfei Zhang, Qiong Yang, Xu Zhang, Can Zhang, Xingyue Zhang, Dongxia Lv, Yanling Song, Huapei Chen, Bing Liu, Yao Hu, Jiongyu Huang, Yuesheng |
author_facet | Zhang, Junhui Li, Lingfei Zhang, Qiong Yang, Xu Zhang, Can Zhang, Xingyue Zhang, Dongxia Lv, Yanling Song, Huapei Chen, Bing Liu, Yao Hu, Jiongyu Huang, Yuesheng |
author_sort | Zhang, Junhui |
collection | PubMed |
description | Endothelial cells play a critical role in the process of angiogenesis during skin wound healing. The migration and proliferation of endothelial cells are processes that are initiated by the hypoxic microenvironment in a wound, but the underlying mechanisms remain largely unknown. Here, we identified a novel role for microtubule-associated protein 4 (MAP4) in angiogenesis. We firstly demonstrated that MAP4 phosphorylation was induced in hypoxic endothelial cells; the increase in MAP4 phosphorylation enhanced the migration and proliferation of endothelial cells. We also found that hypoxia (2% O(2)) activated p38/mitogen-activated protein kinase (MAPK) signaling, and we identified p38/MAPK as an upstream regulator of MAP4 phosphorylation in endothelial cells. Moreover, we showed that the promigration and proproliferation effects of MAP4 phosphorylation were attributed to its role in microtubule dynamics. These results indicated that MAP4 phosphorylation induced by p38/MAPK signaling promotes angiogenesis by inducing the proliferation and migration of endothelial cells cultured under hypoxic conditions via microtubule dynamics regulation. These findings provide new insights into the potential mechanisms underlying the initiation of the migration and proliferation of endothelial cells. |
format | Online Article Text |
id | pubmed-6476958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64769582019-04-30 Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation Zhang, Junhui Li, Lingfei Zhang, Qiong Yang, Xu Zhang, Can Zhang, Xingyue Zhang, Dongxia Lv, Yanling Song, Huapei Chen, Bing Liu, Yao Hu, Jiongyu Huang, Yuesheng Front Pharmacol Pharmacology Endothelial cells play a critical role in the process of angiogenesis during skin wound healing. The migration and proliferation of endothelial cells are processes that are initiated by the hypoxic microenvironment in a wound, but the underlying mechanisms remain largely unknown. Here, we identified a novel role for microtubule-associated protein 4 (MAP4) in angiogenesis. We firstly demonstrated that MAP4 phosphorylation was induced in hypoxic endothelial cells; the increase in MAP4 phosphorylation enhanced the migration and proliferation of endothelial cells. We also found that hypoxia (2% O(2)) activated p38/mitogen-activated protein kinase (MAPK) signaling, and we identified p38/MAPK as an upstream regulator of MAP4 phosphorylation in endothelial cells. Moreover, we showed that the promigration and proproliferation effects of MAP4 phosphorylation were attributed to its role in microtubule dynamics. These results indicated that MAP4 phosphorylation induced by p38/MAPK signaling promotes angiogenesis by inducing the proliferation and migration of endothelial cells cultured under hypoxic conditions via microtubule dynamics regulation. These findings provide new insights into the potential mechanisms underlying the initiation of the migration and proliferation of endothelial cells. Frontiers Media S.A. 2019-04-16 /pmc/articles/PMC6476958/ /pubmed/31040780 http://dx.doi.org/10.3389/fphar.2019.00368 Text en Copyright © 2019 Zhang, Li, Zhang, Yang, Zhang, Zhang, Zhang, Lv, Song, Chen, Liu, Hu and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Zhang, Junhui Li, Lingfei Zhang, Qiong Yang, Xu Zhang, Can Zhang, Xingyue Zhang, Dongxia Lv, Yanling Song, Huapei Chen, Bing Liu, Yao Hu, Jiongyu Huang, Yuesheng Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation |
title | Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation |
title_full | Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation |
title_fullStr | Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation |
title_full_unstemmed | Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation |
title_short | Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation |
title_sort | phosphorylation of microtubule- associated protein 4 promotes hypoxic endothelial cell migration and proliferation |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476958/ https://www.ncbi.nlm.nih.gov/pubmed/31040780 http://dx.doi.org/10.3389/fphar.2019.00368 |
work_keys_str_mv | AT zhangjunhui phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT lilingfei phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT zhangqiong phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT yangxu phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT zhangcan phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT zhangxingyue phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT zhangdongxia phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT lvyanling phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT songhuapei phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT chenbing phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT liuyao phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT hujiongyu phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation AT huangyuesheng phosphorylationofmicrotubuleassociatedprotein4promoteshypoxicendothelialcellmigrationandproliferation |